Cancer is not a single disease but a collection of diseases. It is complex and does not readily give up its secrets. Despite the challenges cancer poses, scientists and clinicians continue to hone the way in which they diagnose and treat it.
Modern medicine means that diagnosis rates for many cancers are up, as are survival rates. However, with an estimated 19.3 million new cases of cancer worldwide in 2020, there is still much work to be done.
MNT recently contacted a number of medical experts and researchers and asked them to speak about the aspects of cancer research that they find most exciting. Their answers are fascinating and demonstrate the incredible variety of approaches that scientists are using to understand and combat cancer.
We will start today’s journey into cutting edge oncology with a surprising guest: magnetically responsive bacteria.
“Due to the difficulty of targeting systemically delivered therapeutics for cancer, interest has grown in exploiting biological agents to enhance tumor accumulation,” explained Prof. Simone Schürle-Finke, Ph.D., from ETH Zurich in Switzerland.
In other words, getting cancer drugs to the right place is not as straightforward as one might hope. Prof. Schürle-Finke is among the researchers who are now enlisting the help of specialized bacteria.
She told MNT how scientists have known for “a century” that certain bacteria can colonize tumors and trigger regression. She explained that today, thanks to modern genetic engineering techniques, attenuated bacteria are available that can have a therapeutic effect exactly where this is necessary.
These therapeutic effects include “secretion of toxins, competition for nutrients, and modulation of immune responses.”
However, despite the promise of bacterial cancer therapy, there are still challenges to meet. Delivering the doses to the right place and getting them into the tumor remain ”foremost among challenges hampering clinical translation — only about 1% of a systemically injected dose reaches the tumor,” explained Prof. Schürle-Finke.
To address these challenges, her team at ETH Zurich is using magnetically responsive bacteria.
These so-called magnetotactic bacteria naturally orient themselves “like compass needles to Earth’s magnetic field.”
Although this ability evolved for navigation, scientists are keen to find out whether “magnetic steering or pulling” could allow them to repurpose it for cancer delivery.
In a recent study, Prof. Schürle-Finke and her colleagues used rotating magnetic fields to override the bacteria’s natural propulsion. As the authors of the study explain, they “used swarms of magnetotactic bacteria to create a directable ‘living ferrofluid.’”
These magnetotactic bacteria have a high demand for iron, so once they reach the tumor, as Prof. Schürle-Finke told MNT, they “can metabolically influence cancer cells through starvation from this vital nutrient. We have shown in in vitro models that an increasing number of bacteria induce an upregulation of iron-scavenging receptors and death in cancer cells.”
“By uniting engineering principles and synthetic biology, we aim to provide a new framework for bacterial cancer therapy that addresses a major remaining hurdle by improving the efficiency of bacterial delivery using safe and scalable magnetic stimuli to these promising living therapeutic platforms.”
– Prof. Simone Schürle-Finke, Ph.D.
“Personalized medicine is transforming the landscape of medicine and how healthcare providers can offer and plan personalized care for each of their patients,” believes Dr. Santosh Kesari, Ph.D., director of neuro-oncology at Providence Saint John’s Health Center in Santa Monica, CA.
Dr. Kesari is also chair of the Department of Translational Neurosciences at Saint John’s Cancer Institute and regional medical director for the Research Clinical Institute of Providence Southern California.
Describing personalized medicine, Dr. Kesari said, “It is an approach for disease prevention and treatment that takes into account biological, genetic, behavioral, environmental, and social risk factors that are unique to every individual.”
He continued, “Personalized medicine is rooted in early detection and prevention; integrating data from genomics and other advanced technologies; digital health monitoring; and incorporating the latest medical innovations for optimizing outcomes.”
“This is becoming very apparent in oncology, where genetic testing for tumor mutations and predispositions is increasingly being utilized and showing more value in using targeted drugs more wisely and improving outcomes.”
Dr. Santosh Kesari, Ph.D.
Some personalized cancer approaches are already in use, such as EGFR, HER2, and NTRK inhibitors and the “super personalized” CAR-T cells.
According to Dr. Kesari, the future of personalization is bright, and “progress has only accelerated in the past 5 years.”
Continuing with the personalization theme, Dr. Robert Dallmann from Warwick Medical School at Warwick University in the United Kingdom talked with us about chronotherapy:
“Propelled by the 2017 Nobel Prize in Medicine or Physiology [going] to three circadian biologists for uncovering the molecular mechanism of circadian biological clocks, cancer chronotherapy is gaining critical momentum to enter mainstream oncology — especially in the context of personalized medicine.”
Dr. Dallmann explained that “many key physiological processes in the cells of our body are modulated in a daily fashion by the circadian clock. These cellular clocks are disrupted in some tumors but not in others.”
“Interestingly, a functional clock in the tumor predicts the survival time of patients, which has been shown for brain as well as breast tumors.”
Therefore, he explained, if scientists could “determine the clock status in solid tumors,” it would allow doctors to more easily determine whether a patient is at high or low risk. It might also help guide therapy.
“There is great potential in optimizing treatment plans with existing drugs by taking into account the interaction with the circadian system of the patient,” continued Dr. Dallmann.
“More recently, the circadian clock mechanism itself has been proposed as a novel treatment target in glioblastoma.” The authors of the glioblastoma study concluded that “pharmacologic targeting of circadian networks specifically disrupted cancer stem cell growth and self-renewal.”
However, “whether this might be generalized to many solid tumors or even other chronic diseases remains to be elucidated,” said Dr. Dallmann.
“In summary,” he told MNT, “circadian clocks have long been recognized to modulate chronic disease on many levels. The increased mechanistic understanding has the potential to improve diagnosis and existing treatments of cancer, as well as develop a new class of clock-targeting treatments.”
Dr. Chung-Han Lee is a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. He is also a member of the Kidney Cancer Association’s Medical Steering Committee. He talked us through recent advances in the treatment of kidney cancer.
“The development and subsequent regulatory approval of combination immunotherapy for patients with metastatic kidney cancer have led to transformative change in the lives of many patients and are the hallmark of how greater scientific understanding has impacted cancer care,” Dr. Lee told MNT.
“Prior to 2005, treatment for metastatic kidney cancer was very limited, with most patients passing away in less than 1 year despite undergoing treatment.” According to Dr. Lee, the development of antiangiogenic drugs that inhibit the growth of new blood vessels “was among the first breakthroughs to improve the outcomes for patients.”
However, even with antiangiogenic drugs, “most patients ultimately developed resistance to treatment, and 18 months was considered a long-term response.” Next came immunotherapies.
“Prior to the development of antiangiogenic medications, it was known that kidney cancer could be treated by activating the immune system to better recognize the disease. However, the tools to activate the immune system were often very nonspecific. Therefore, responses to these early immunotherapies were rare, and the side effects related to treatment were not only burdensome but also could be life threatening.”
“With recent advances in immunotherapy, we have demonstrated that more targeted immunotherapies that activate specific immune checkpoints are not only possible but can have substantially increased activity against disease.”
“Two emerging treatment approaches have now become the new standard of care for kidney cancer: dual immunotherapies (such as ipilimumab/nivolumab) or combinations of antiangiogenic targeted therapies with immunotherapies (such as axitinib/pembrolizumab).”
“In patients treated with ipilimumab and nivolumab, over 50% remain alive at 4 years, and with some [combined antiangiogenic and immunotherapy approaches], nearly 50% of patients remain on their initial therapy at 2 years.”
Despite these advances, Dr. Lee is far from complacent, telling us that “there remains considerable work to be done. […] Unfortunately, in 2021, for most patients, kidney cancer remains fatal. Even for those who have outstanding responses to treatment, most still require ongoing systemic therapy.”
“With the rapid improvements in treatments, the development of correlative biomarkers, and the improved biologic understanding of the disease, we have only started to entertain the possibility of curative, time-limited therapy.”
“Building on the sacrifices of patients and caregivers and the hard work of clinicians, research staff, and scientists, a cure may, one day, be a reality for our patients,” he concluded.
“Our study from late 2020 has shown that the antidepressant sertraline helps to inhibit the growth of cancer cells in mice,” Prof. Kim De Keersmaecker from KU LEUVEN in Belgium told MNT.
“Other studies had already indicated that the commonly used antidepressant has anticancer activity, but there was no explanation for the cause of this. We’ve been able to demonstrate that sertraline inhibits the production of serine and glycine, causing decreased growth of cancer cells.”
Cancer cells and healthy cells are often reliant on the amino acids serine and glycine, which they extract from their environment. However, certain cancer cells produce serine and glycine within the cell. They can become “addicted” to this production.
This internal production of serine and glycine requires certain enzymes, and these enzymes have become targets for cancer researchers. Preventing them from functioning can “starve” the cancer cells.
Previous studies have identified inhibitors of serine/glycine synthesis enzymes, but none have reached the clinical trial stage. As the authors of a KU LEUVEN study note, because “sertraline is a clinically used drug that can safely be used in humans,” it might make a good candidate.
Prof. De Keersmaecker explained that “when used with other therapeutics, the drug strongly inhibited the growth of cancer cells in the mice.”
The authors of the study concluded: “Collectively, this work provides a novel and cost efficient treatment option for the rapidly growing list of serine/glycine synthesis-addicted cancers.”
Christy Maksoudian from the NanoHealth & Optical Imaging Group team at KE LEUVEN is excited about the promise of nanotechnology for the treatment of cancer. She told MNT that “because of the unique properties that emerge at such a small scale, nanoparticles can be designed in a multitude of ways to exhibit specific behaviors” in organisms.
Currently, she explained, many “available nanoformulations in the clinic are composed of organic materials because of their biocompatibility and safety.” In this context, “organic” refers to compounds that include carbon.
However, she explains that inorganic nanomaterials, which do not contain carbon, also hold promise for cancer treatment because they “possess further functionalities.”
“For instance, some magnetic nanoparticles, such as those of superparamagnetic iron oxide, can be magnetically guided toward the tumor, while gold nanoparticles generate heat upon exposure to near-infrared light and can, therefore, be used for photothermal therapy (via tumor tissue ablation).”
In short, it is possible to introduce
“Because of the potential of such broad range of nanomaterial designs, there are always novel cancer therapies being developed.”
– Christy Maksoudian
“I am excited to take part in this movement with my work on
Maksoudian told MNT that these nanoparticles “exploit intrinsic metabolic differences between cancer cells and healthy cells to induce high levels of toxicity in cancer cells while only causing reversible damage in healthy tissue.”
“The fact that such cancer-selective properties can arise due to minor modifications of the nanoparticles at the nanoscale is truly extraordinary and reaffirms the significant role that nanomedicine can play in expanding the treatment landscape for oncology.”
Cancer is complex, so approaches to its treatment must match that complexity. As the summaries above demonstrate, scientists are not short on ingenuity, and the battle against cancer continues at pace.